Development of gene therapy for cancer has been advancing in recent years. Hitherto, the present inventors have developed gene therapy vectors using the Sendai virus (SeV). SeV is a virus of the paramyxovirus family and belongs to a group of viruses comprising nonsegmented negative strand RNA as its genome. Paramyxoviral vectors enable high transfection rate and overexpression of foreign genes, and are expected to serve as gene therapy vectors for cancer. To date, a number of cancer therapies using paramyxovirus have been performed. For example, BHK21 cells infected with Mumps virus were observed to show anti-tumor effects in tumor-bearing nude mice (Minato, N. et al., J. Exp. Med. 149, 1117-1133, 1979). Similarly, antitumor effects have been reported in other paramyxoviruses. Recently, the antitumor effects of fusogenic proteins are attracting attention. Galanis et al. reported that cancer cells infected with an adenoviral vector that carries the F and HN proteins of measles virus form syncytia, resulting in antitumor effects in vivo (Galanis, E. et al., Hum. Gene Ther. 12, 811-821, 2001).
Needless to say, cancer that does not metastasize can be treated by surgically removing that portion, and metastatic cancer and malignant cancer are considered synonymous. Infiltrating metastatic cancers are known to overexpress matrix metalloprotease (MMP) and/or plasminogen activators (uPA, tPA) (Cox, G., and O'Byrne, K. J., Anticancer Res. 21, 4207-4219, 2001; Andreasen, P. A. et al., Cell Mol. Life. Sci. 57, 25-40, 2000). This overexpression is believed to occur due to the fact that infiltration and metastasis become possible only after the surrounding extracellular matrix (ECM), which is an obstacle preventing cell transposition during metastasis and infiltration of cancer cells, is degraded through the expression of enzymes (MMP, uPA, tPA) that degrade the ECM by cancer.
On the other hand, three problems have been raised regarding gene therapies for cancer. Firstly, since the gene transfer efficiency into cancer cells is low and gene transfer to the core of a solid cancer cannot be easily accomplished, genes cannot be transfected to the entire cancer. Accordingly, remaining cancer cells start to proliferate again, which leads to recurrence. Secondly, genes are transfected not only to cancer cells but also to normal cells. Toxic genes injure the normal cells, thereby resulting in increased side-effects. Thirdly, the occurrence of infiltration and metastasis as the cancer becomes malignant is a problem in all kinds of cancer therapy. To date, a vectors that solves these problems has not yet been developed.